Mechanisms of serpin inhibition

Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity

Volumn , Issue , 2007, Pages 67-100

  Gettins, Peter G W ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84967495964     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1142/9789812707543_0003     Document Type: Chapter

References (102)

1. BodeW and Huber R(1992) Natural protein proteinase inhibitors and their interaction with proteinases. Eur J Biochem 204:433-451.
2. Estell DA, Wilson KA and Laskowski M(1980) Thermodynamics and kinetics of the hydrolysis of the reactive-site peptide bond in pancreatic trypsin inhibitor (Kunitz) by Dermasterias imbricata trypsin 1. Biochemistry 19:131-137.
3. Gettins PGW(2002) Serpin structure, mechanism and function. Chem Rev 102:4751-4804.
4. Rubin H, Wang ZM, Nickbarg EB, McLarney S, Naidoo N, Schoenberger OL, Johnson JL and Cooperman BS(1990) Cloning expression, purification, and biological activity of recombinant native and variant human α1-antichymotrypsin. J Biol Chem 265:1199-1207.
5. Patston PA, Gettins P, Beechem J and Schapira M(1991) Mechanism of serpin action: Evidence that C1 inhibitor functions as a suicide substrate. Biochemistry 30:8876-8882.
6. Dementiev A, Simonovic M, Volz K and Gettins PGW(2003) Canonical inhibitor-like interactions explain reactivity of α1-proteinase inhibitor Pittsburgh and antithrombin with proteinases. J Biol Chem 278:37881-37887.
7. Ye S, CechAL, Belmares R, Bergstrom RC, TongY, Corey DR, KanostMand Goldsmith EJ(2001) The structure of a Michaelis serpin-protease complex. Nat Struct Biol 8:979-983.
8. Baglin TP, Carrell RW, Church FC, Esmon CT and Huntington JA(2002) Crystal structure of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism. Proc Natl Acad Sci USA 99:11079-11084.
9. Dementiev A, Petitou M, Herbert JM and Gettins PGW(2004) The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity. Nat Struct Mol Biol 11:863-867.
10. Li W, Johnson DJ, Esmon CT and Huntington JA(2004) Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol 11:857-862.
11. Johnson DJ, LiW, AsamsTE and Huntington JA(2006)Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation. EMBO J 25:2029-2037.
12. Peterson FC, GordonNCand GettinsPGW(2000) Formation of non-covalent serpin-proteinase complex involves no conformational change in the serpin. Use of 1H-15N HSQC NMR as a sensitive non-perturbing monitor of conformation. Biochemistry 39:11884-11892.
13. Dobó J and Gettins PGW(2004) α1-Proteinase inhibitor forms initial noncovalent and final covalent complexes with elastase analogously to other serpin-proteinase pairs, suggesting a common mechanism of inhibition. J Biol Chem 274:9264-9269.
14. Jin L, Abrahams JP, Skinner R, Petitou M, Pike RN and Carrell RW(1997) The anticoagulant activation of antithrombin by heparin. Proc Natl Acad Sci USA 94:14683-14688.
15. Hopkins PCR and Stone SR(1995) The contribution of the conserved hinge region residues of α1-antitrypsin to its reaction with elastase. Biochemistry 34:15872-15879.
16. O’Malley KM and Cooperman BS(2001) Formation of the covalent chymotrypsin:Antichymotrypsin complex involves no large-scale movement of the enzyme. J Biol Chem 276:6631-6637.
17. LuoY, ZhouY and Cooperman BS(1999) Antichymotrypsin interaction with chymotrypsin. Intermediates on the way to inhibited complex formation. J Biol Chem 274:17733-17741.
18. Beatty K, Bieth J and Travis J(1980) Kinetics of association of serine proteinases with native and oxidized α-1-proteinase inhibitor and α-1- antichymotrypsin. J Biol Chem 255:3931-3934.
19. Chen VC, Chao L and Chao J(2000) Roles of the P1, P2, and P3 residues in determining inhibitory specificity of kallistatin toward human tissue kallikrein. J Biol Chem 275:38457-38466.
20. Stump DC, Thienpont M and Collen D(1986) Purification and characterization of a novel inhibitor of urokinase from human urine. Quantitation and preliminary characterization in plasma. J Biol Chem 261:12759-12766.
21. Frazer JK, Jackson DG, Gaillard JP, Lutter M, Liu YJ, Banchereau J, Capra JD and Pascual V(2000) Identification of centerin:A novel human germinal center B cell-restricted serpin. Eur J Immunol 30:3039-3048.
22. Han X, Fiehler R and Broze GJ Jr(2000) Characterization of the protein Z-dependent protease inhibitor. Blood 96:3049-3055.
23. Remold-O’Donnell E, Chin J and AlbertsM(1992) Sequence and molecular characterization of human monocyte/neutrophil elastase inhibitor. Proc Natl Acad Sci USA 89:5635-5639.
24. Ye RD, Wun T and Sadler JE(1987) cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta. J Biol Chem 262:3718-3725.
25. Schick C, Pemberton PA, Shi GP, Kamachi Y, Cataltepe S, Bartuski AJ, Gornstein ER, Brömme D, Chapman HA and Silverman GA(1998) Crossclass inhibition of the cysteine proteinases cathepsins K, L, and S by the serpin squamous cell carcinoma antigen 1: A kinetic analysis. Biochemistry 37:5258-5266.
26. Schick C, Kamachi Y, Bartuski AJ, Çataltepe S, Schechter NM, Pemberton PA and Silverman GA(1997) Squamous cell carcinoma antigen 2 is a novel serpin that inhibits the chymotrypsin-like proteinases cathepsin G and mast cell chymase. J Biol Chem 272:1849-1855.
27. Coughlin P, Sun JR, Cerruti L, Salem HH and Bird P(1993) Cloning and molecular characterization of a human intracellular serine proteinase inhibitor. Proc Natl Acad Sci USA 90:9417-9421.
28. Miyata T, Nangaku M, Suzuki D, Inagi R, Uragami K, Sakai H, Okubo K and Kurokawa K(1998) A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy. J Clin Invest 102:828-836.
29. Dahlen JR, Jean F, Thomas G, Foster DC and Kisiel W(1998) Inhibition of soluble recombinant furin by human proteinase inhibitor 8. J Biol Chem 273:1851-1854.
30. Sprecher CA, Morgenstern KA, Mathewes S, Dahlen JR, Schrader SK, Foster DC and Kisiel W(1995) Molecular cloning, expression, and partial characterization of two novel members of the ovalbumin family of serine proteinase inhibitors. J Biol Chem 270:29854-29861.
31. Dahlen JR, Foster DC and Kisiel W(1997) Human proteinase inhibitor 9 (P19) is a potent inhibitor of subtilisinA. Biochem Biophys Res Commun 238:329-333.
32. Riewald M and Schleef RR(1995) Molecular cloning of bomapin (protease inhibitor 10), a novel human serpin that is expressed specifically in the bone marrow. J Biol Chem 270:26754-26757.
33. Askew YS, Pak SC, Luke CJ, Askew DJ, Cataltepe S, Mills DR, Kato H, Lehoczk YJ, Dewar K, Birren B and Silverman GA (2001) SERPINB12 is a novel member of the human ov-serpin family that is widely expressed and inhibits trypsin-like serine proteinases. J Biol Chem 276: 49320-49330.
34. Welss T, Sun J, Irving JA, Blum R, Smith AI, Whisstock JC, Pike RN, von Mikecz A, Ruzicka T, Bird PI and Abts HF(2003) Hurpin is a selective inhibitor of lysosomal cathepsinLand protects keratinocytes from ultravioletinduced apoptosis. Biochemistry 42:7381-7389.
35. Olson ST and Björk I (1991) Predominant contribution of surface approximation to the mechanism of heparin acceleration of the antithrombinthrombin reaction. Elucidation from salt concentration effects. J Biol Chem 266: 6353-6364.
36. Sheehan JP, Wu Q, Tollefsen DM and Sadler JE(1993) Mutagenesis of thrombin selectively modulates inhibition by serpins heparin cofactor II and antithrombin III. Interaction with the anion-binding exosite determines heparin cofactor II specificity. J Biol Chem 268:3639-3645.
37. Lawrence D, Strandberg L, Grundström T and Ny T(1989) Purification of active human plasminogen activator inhibitor-1 from Escherichia coli. Comparison with natural and recombinant forms purified from eucaryotic cells. Eur J Biochem 186:523-533.
38. ScottRW, Bergman BL, BajpaiA, HershRT, Rodriguez H, Jones BN, Barreda C, Watts S and Baker JB (1985) Protease nexin. Properties and a modified purification procedure. J Biol Chem 260: 7029-7034.
39. Wiman B and Collen D(1978) On the kinetics of the reaction between human antiplasmin and plasmin. Eur J Biochem 84:573-578.
40. Sim RB, Arlaud G and Colomb M(1980) Kinetics of reaction of human C1- inhibitorwith the human complement system proteases C1r and C1s. Biochim Biophys Acta 612:433-449.
41. Krueger SR, Ghisu GP, Cinelli P, Gschwend TP, Osterwalder T, Wolfer DP and Sonderegger P(1997) Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse. J Neurosci 17:8984-8996.
42. Ozaki K, NagataM, Suzuki M, Fujiwara T, MiyoshiY, Ishikawa O, Ohigashi H, Imaoka S, Takahashi E and NakamuraY(1998) Isolation and characterization of a novel human pancreas-specific gene, pancpin, that is down-regulated in pancreatic cancer cells. Genes Chromosomes Cancer 22:179-185.
43. Owen MC, Brennan SO, Lewis JH and Carrell RW(1983) Mutation of antitrypsin to antithrombin. α1-Antitrypsin Pittsburgh (358 Met Arg), a fatal bleeding disorder. N Engl J Med 309:694-698.
44. ChuangY-J, Gettins PGW and Olson ST(1999) Importance of the P2 glycine of antithrombin in target proteinase specificity, heparin activation and the efficiency of proteinase trapping as revealed by a P2 Gly Pro mutation. J Biol Chem 274:28142-18149.
45. Bianchini EP, Louvain VB, Marque P-E, Juliano MA, Juliano L and Le Bonniec BF(2002) Mapping of the catalytic groove preferences of factor Xa reveals an inadequate selectivity for its macromolecule substrates. J Biol Chem 277:20527-20534.
46. Dufour EK, Denault J-B, Bissonnette L, Hopkins PCR, Lavigne P and Leduc R(2001) The contribution of arginine residues within the P6-P1 region of α1-antitrypsin to its reaction with furin. J Biol Chem 276:38971-38979.
47. Chaillan-Huntington CE, GettinsPGW, Huntington JAand Patston PA(1997) The P6-P2 region of serpins is critical for proteinase inhibition and complex stability. Biochemistry 36:9562-9570.
48. Izaguirre G and Oison ST(2006) Residues Tyr253 and Glu255 in strand 3 of beta-sheet C of antithrombin are key determinants of an exosite made accessible by heparin activation to promote rapid inhibition of factors Xa and IXa. J Biol Chem 281:13424-13432.
49. Rubin H, Plotnick M, Wang Z, Liu X, Zhong Q, Schechter NM and Cooperman BS(1994) Conversion of α1-antichymotrypsin into a human neutrophil elastase inhibitor: Demonstration of variants with different association rate constants, stoichiometries of inhibition, and complex stabilities. Biochemistry 33:7627-7633.
50. Matheson NR, van Halbeek H and Travis J(1991) Evidence for a tetrahedral intermediate complex during serpin-proteinase interactions. J Biol Chem 266:13489-13491.
51. Lawrence DA, Ginsburg D, Day DE, Berkenpas MB, Verhamme IM, Kvassman J-O and Shore JD(1995) Serpin-protease complexes are trapped as stable acyl-enzyme intermediates. J Biol Chem 270:25309-25312.
52. Huntington JA, Read RJ and CarrellRW(2000) Structure of a serpin-protease complex shows inhibition by deformation. Nature (London) 407: 923-926.
53. Dementiev A, Dobo J and Gettins PGW(2006) Active site distortion is sufficient for proteinase inhibtion by serpins. Structure of the covalent complex of alpha-1 proteinase inhibitor with porcine pancreatic elastase. J Biol Chem 281:3452-3457.
54. Stratikos E and Gettins PGW(1998) Mapping the serpin-proteinase complex using single cysteine variants of α-proteinase inhibitor Pittsburgh. J Biol Chem 273:15582-15589.
55. Stratikos E and Gettins PGW(1999) Formation of the covalent serpinproteinase complex involves translocation of the proteinase by more than 70Å and full insertion of the reactive center loop into β-sheet A. Proc Natl Acad Sci USA 96:4808-4813.
56. Peterson FC and Gettins PGW(2001) Insight into the mechanism of serpin-proteinase inhibition from 2D [1H-15N] NMR studies of the 69kDa α1-proteinase inhibitor Pittsburgh-trypsin covalent complex. Biochemistry 40:6284-6292.
57. Backovic M, Stratikos E, Lawrence DA and Gettins PGW(2002) Structural similarity of the covalent complexes formed between the serpin plasminogen activator inhibitor-1 and the arginine-specific proteinases trypsin, LMW urokinase, HMW urokinase and tPA: Use of site-specific fluorescent probes of local environment. Protein Sci 11:1182-1191.
58. NaY-R and Im H(2005) The length of the reactive center loop modulates the latency transition of plasminogen activator inhibitor-1. Protein Sci 14:55-63.
59. Im H, Ahn HY andYuMH(2000) Bypassing the kinetic trap of serpin protein folding by loop extension. Protein Sci 9:1497-1502.
60. Stein PE and Carrell RW(1995) What do dysfunctional serpins tell us about molecular mobility and disease? Nat Struct Biol 2:96-113.
61. Hood DB, Huntington JA and Gettins PGW(1994) α1-Proteinase inhibitor variant T345R. Influence of P14 residue on substrate and inhibitory pathways. Biochemistry 33:8538-8547.
62. Lawrence DA, Olson ST, Muhammad S, Day DE, Kvassman J-O, Ginsburg D and Shore JD(2000) Partitioning of serpin-proteinase reactions between stable inhibition and substrate cleavage is regulated by the rate of serpin reactive center loop insertion into β-sheet A*. J Biol Chem 275:5839-5844.
63. Huntington JA, Fan B, Karlsson KE, Deinum J, Lawrence DA and Gettins PGW(1997) Serpin conformational change in ovalbumin. Enhanced reactive center loop insertion through hinge region mutations. Biochemistry 36:5432-5440.
64. Yamasaki M, Arii Y, Mikami B and Hirose M(2002) Loop-inserted and thermostabilized structure of P1-P1' cleaved ovalbumin mutant R339T. J Mol Biol 315:113-120.
65. Arii Y and Hirose M(2002) Probing the serpin structural-transition mechanism in ovalbumi mutant R339T by proteolytic-cleavage kinetics of the reactive centre loop. Biochem J 363:403-409.
66. Takahashi N, Terakado K, Nakamura G, SoekmadjiC, MasuokaT, Yamasakio Mand HiroseM(2005) Dynamic mechanism for the serpin loop insertion as revealed by quantitative kinetics. J Mol Biol 348:409-418.
67. Plotnick MI, Mayne L, Schechter NM and Rubin H(1996) Distortion of the active site of chymotrypsin complexed with a serpin. Biochemistry 35:7586-7590.
68. Futamura A, Stratikos E, Olson ST and Gettins PGW(1998) Change in environment of the P1 side chain upon progression from the Michaelis complex to the covalent serpin-proteinase complex. Biochemistry 37:13110-13119.
69. Calugaru SV, Swanson R and Olson ST(2001) The pH dependence of serpinproteinase complex dissociation reveals a mechanism of complex stabilization involving inactive and active conformational states of the proteinase which are perturbable by calcium. J Biol Chem 276:32446-32455.
70. Shin J-S and Yu M-H(2002) Kinetic dissection of α1-antitrypsin inhibition mechanism. J Biol Chem 277:11629-11635.
71. Egelund R, PetersenTE andAndreasen PAA(2001) serpin-induced extensive proteolytic susceptibility of urokinase-type plasminogen activator implicates distortion of the proteinase substrate binding pocket and oxyanion hole in the serpin inhibitory mechanism. Eur J Biochem 268:673-685.
72. FishWW, OrreKand Björk I(1979) Routes of thrombin action in the production of proteolytically modified, secondary forms of antithrombin-thrombin complex. Eur J Biochem 101:39-44.
73. Cooperman BS, Stavridi E, Nickbarg E, Rescorla E, Schechter NM and Rubin H(1993) Antichymotrypsin interaction with chymotrypsin - partitioning of the complex. J Biol Chem 268:23616-23625.
74. Stavridi ES, O’Malley K, Lukacs CM, Moore WT, Lambris JD, Christianson DW, Rubin H and Cooperman BS(1996) Structural change in α-chymotrypsin induced by complexation with α1-antichymotrypsin as seen by enhanced sensitivity to proteolysis. Biochemistry 35:10608-10615.
75. Kaslik G, Patthy A, Bálint M and Gráf L(1995) Trypsin complexed with α1-proteinase inhibitor has an increased structural flexibility. FEBS Lett 370:179-183.
76. Kaslik G, Kardos J, Szabó L, Závodszky P, Westler WM, Markley JL and Gráf L(1997) Effects of serpin binding on the target proteinase: Global stabilization, localized increased structural flexibility, and conserved hydrogen bonding at the active site. Biochemistry 36:5455-5474.
77. Hervé M and Ghélis C(1991) Conformational stability of the covalent complex between elastase and α1-proteinase inhibitor. Arch Biochem Biophys 285:142-146.
78. Irving JA, Pike RN, Lesk AM and Whisstock JC(2000) Phylogeny of the serpin superfamily: Implications of patterns of amino acid conservation for structure and function. Genome Res 10:1845-1864.
79. SimonovicM, Gettins PGW andVolz K(2000) Crystal structure of viral serpin crmA provides insights into its mechanism of cysteine proteinase inhibition. Protein Sci 9:1423-1427.
80. Zhou A, Carrell RW and Huntington JA(2001) The serpin inhibitory mechanism is critically dependent on the length of the reactive center loop. J Biol Chem 276:27541-27547.
81. Plotnick MI, Rubin H and Schechter NM(2002) The effects of reactive site location on the inhibitory properties of the serpin alpha 1-antichymotrypsin. J Biol Chem 277:29927-29935.
82. Boudier C and Bieth JG(2001) The reaction of serpins with proteinases involves important enthalpy changes. Biochemistry 40:9962-9967.
83. Boudier C, Gils A, Declerck PJ and Bieth JG(2005) The conversion of active to latent plasminogen activator inhibitor-1 is an energetically silent event. Biochem J 88:2848-2854.
84. Gettins PGW(2002) The F-helix of serpins plays an essential, active role in the proteinase inhibition mechanism. FEBS Lett 523:2-6.
85. PicardV, Marque P-E, Paolucci F, AiachMand Le Bonniec BF(1999) Topology of the stable serpin-protease complexes revealed by an autoantibody that fails to react with the monomeric conformers of antithrombin. J Biol Chem 274:4586-4593.
86. Vleugels N, Gils A, Bijnens A-P, Knockaert I and Declerck P(2000) The importance of helix F in plasminogen activator inhibitor-1. Biochim Biophys Acta 1476:20-26.
87. WindT, Jensen JK, DupontDM, Kulig P andAndreasen PA(2003) Mutational analysis of plasminogen activator inhibitor-1. Interactions of α-helix F and its neighbouring structural elements regulates the activity and the rate of latency transition. Eur J Biochem 270:1680-1688.
88. Plotnick MI, Samakur MMWZ, Liu X, Rubin H, Schechter NM and Selwood T(2002) Heterogeneity in serpin-proteinase complexes as demonstrated by differences in the mechanism of complex breakdown. Biochemistry 41:334-342.
89. Renatus M, Zhou Q, Stennike HR, Snipas SJ, Turk D, Bankston LA, Liddington RC and Salvesen GS(2000) Crystal structure of the apoptotic suppressor CrmA in its cleaved form. Structure 8:789-797.
90. Tesch LD, RaghavendraMP, Bedsted-FaarvangT, GettinsPGWand OlsonST(2005) Specificity and reactive loop length requirements for CrmA inhibition of serine proteases. Protein Sci 14:533-542.
91. Raghavendra MP, Bedsted T, Zhang W, Froelich CJ, Thornberry N, Gettins PGW and Olson ST(2006) Evidence for similar extents of protease translocation in crmA complexes with granzyme B and caspase-1, submitted.
92. Xu G, Cirilli M, HuangY, Rich RL, Myszka DG andWu H(2001) Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex. Nature (London) 410:494-497.
93. Kvassman JO, Verhamme I and Shore JD(1998) Inhibitory mechanism of serpins:loop insertion forces acylation of plasminogen activator by plasminogen activator inhibitor-1. Biochemistry 37:15491-15502.
94. Schwartz BS and España F(1999) Two distinct urokinase-serpin interactions regulate the initiation of cell-surface-associated plasminogen activation. J Biol Chem 274:15278-15283.
95. Shieh B-H, Potempa J and Travis J(1989) The use of α2-antiplasmin as a model for the demonstration of complex reversibility in serpins. J Biol Chem 264:13420-13423.
96. Stark KR and James AA(1996) Salivary gland anticoagulants in culicine and anopheline mosquitoes (Diptera: Culicidae). J Med Entomol 33:645-650.
97. Stark KR and James AA(1998) Isolation and characterization of the gene encoding a novel factor Xa-directed anticoagulant from the yellow fever mosquito, Aedes aegypti. J Biol Chem 273:20802-20809.
98. Stark KR and JamesAA (1995)A factor Xa-directed anticoagulant from the salivary glands of the yellow fever mosquito Aedes aegypti. Exp Parasitol 81:321-331.
99. Ngamkitidechakul A, Warejcka DJ, Burke JM, O’Brien WJ and Twining SS(2003) Sufficiency of the reactive site loop of maspin for induction of cell-matrix adhesion and inhibition of cell invasion. Conversion of ovalbumin to a maspin-like molecule. J Biol Chem 278:31796-31806.
100. McGowen R, Biliran HJ, Sager R and Sheng S(2000) The surface of prostate carcinoma DU145 cells mediates the inhibition of urokinase-type plasminogen activator by maspin. Cancer Res 60:4771-4778.
101. Bass R, Fernandéz A-MM and Ellis V(2002) Maspin inhibits cell migration in the absence of protease inhibitory activity. J Biol Chem 277:46845-46848.
102. Mellet P, Michels B and Bieth JG(1996) Heat-induced conversion of ovalbumin into a proteinase inhibitor. J Biol Chem 271:30311-30314.